title: Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.
abstract: Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process, but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphologic changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B-cell subset. We demonstrate that the disruption is entirely dependent on type I interferon (IFN). At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such rerouted lymphocyte trafficking may impact the development of B-cell immunity to systemic viral pathogens.
authors.affiliation: Center for Integrated Protein Science Munich, Division of Clinical Pharmacology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany;
authors.forename: Simon
authors.initials: S
authors.lastname: Heidegger
authors.forename: David
authors.initials: D
authors.lastname: Anz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stephan
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bohn
authors.forename: Tina
authors.initials: T
authors.lastname: Herbst
authors.forename: Wolfgang Peter
authors.initials: WP
authors.lastname: Fendler
authors.forename: Nina
authors.initials: N
authors.lastname: Suhartha
authors.forename: Nadja
authors.initials: N
authors.lastname: Sandholzer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
authors.forename: Christian
authors.initials: C
authors.lastname: Hotz
authors.forename: Katharina
authors.initials: K
authors.lastname: Eisenächer
authors.forename: Susanne
authors.initials: S
authors.lastname: Radtke-Schuller
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000276:immunology; D054243:Vesicular Stomatitis / Q000276:immunology* / Q000473:pathology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D012367:RNA, Viral